The experiments described in this proposal are designed to clarify the mechnisms of platelet participation in inflammation. To do this, three areas will be studied: 1) The mechanisms of platelet stimulation by inflammatory stimuli; monosodium urate crystals are potent phlogistic agents in man and occur pathologically in human gout. These crystals stimulate platelets in vitro. To elucidate the mechanism(s) whereby these agents stimulate platelets, platelet surface proteins which interact with urate crystals will be characterized. In addition, the roles of C1 and fibronectin, which have been proposed to be platelet surface receptors, in platelet stmulation by urate crystals will be evaluated. 2) The mechanism of secretion of platelet "alpha granule constituents: Platelet alpha granules contain a variety of proteins which may be involved in the production of or response to tissue injury. We will elucidate the mechanism whereby the contents of these granules are released from stimulated platelets. 3) Detection of platelet activation and localization in vivo in experimentally induced inflammation.